ApoIII and the treatment and diagnosis of diabetes
The present invention provides methods of identifying candidate compounds for the treatment of type I diabetes comprising contacting pancreatic β cells with an amount of apolipoprotein CIII (“apoCIII”) effective to increase intracellular calcium concentration, in the presence of one or more test compounds, and identifying those test compounds that inhibit an apoCIII-induced increase in intracellular calcium concentration in the pancreatic β cells. The present invention also provides methods for treating patients with type I diabetes comprising administering to the patient an amount effective of an inhibitor of apoCIII to reduce apoCIII-induced increase in intracellular calcium concentration in pancreatic β cells.
1. A method for diagnosing Type 1 diabetes in a subject, comprising:
(a) measuring an amount of sialylated apoCIII in a blood serum sample from the subject;
(b) comparing the amount of sialylated apoCIII measured in step (a) with an amount of sialylated apoCIII in a control blood serum sample; and
(c) diagnosing those subjects with an elevated amount of sialylated apoCIII measured in step (a) relative to the amount of sialylated apoCIII in the control blood serum sample as having Type 1 diabetes.
2. The method of claim 1 , wherein the sialylated apoCIII is mono-sialylated apoCIII.
3. The method of claim 1 , wherein the sialylated apoCIII is di-sialylated apoCIII.
4. The method of claim 1 , wherein the sialylated apoCIII is both mono- and di-sialylated apoCIII.